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Article: Lipocalin-2 induces NLRP3 inflammasome activation via HMGB1 induced TLR4 signaling in heart tissue of mice under pressure overload challenge

TitleLipocalin-2 induces NLRP3 inflammasome activation via HMGB1 induced TLR4 signaling in heart tissue of mice under pressure overload challenge
Authors
KeywordsLipocalin-2
Pressure overload
NLRP3 inflammasome
HMGB1
Toll-like receptor (TLR)-4
Issue Date2017
PublisherE-Century Publishing Corporation. The Journal's web site is located at http://www.ajtr.org
Citation
American Journal of Translational Research, 2017, v. 9 n. 6, p. 2723-2735 How to Cite?
AbstractLipocalin-2 (also known as NGAL) levels are elevated in obesity and diabetes yet relatively little is known regarding effects on the heart. We induced pressure overload (PO) in mice and found that lipocalin-2 knockout (LKO) mice exhibited less PO-induced autophagy and NLRP3 inflammasome activation than Wt. PO-induced mitochondrial damage was reduced and autophagic flux greater in LKO mice, which correlated with less cardiac dysfunction. All of these observations were negated upon adenoviral-mediated restoration of normal lipocalin-2 levels in LKO. Studies in primary cardiac fibroblasts indicated that lipocalin-2 enhanced priming and activation of NLRP3-inflammasome, detected by increased IL-1β, IL-18 and Caspase-1 activation. This was attenuated in cells isolated from NLRP3- deficient mice or upon pharmacological inhibition of NLRP3. Furthermore, lipocalin-2 induced release of HMGB1 from cells and NLRP3-inflammasome activation was attenuated by TLR4 inhibition. We also found evidence of increased inflammasome activation and reduced autophagy in cardiac biopsy samples from heart failure patients. Overall, this study provides new mechanistic insight on the detrimental role of lipocalin-2 in the development of cardiac dysfunction.
Persistent Identifierhttp://hdl.handle.net/10722/248507
ISSN
2019 Impact Factor: 3.375
2015 SCImago Journal Rankings: 1.442
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorSong, E-
dc.contributor.authorJahng, JW-
dc.contributor.authorChong, LP-
dc.contributor.authorSung, HK-
dc.contributor.authorHan, M-
dc.contributor.authorLuo, C-
dc.contributor.authorWu, D-
dc.contributor.authorBoo, S-
dc.contributor.authorHinz, B-
dc.contributor.authorCooper, MA-
dc.contributor.authorRobertson, AA-
dc.contributor.authorBerger, T-
dc.contributor.authorMak, TW-
dc.contributor.authorGeorge, I-
dc.contributor.authorSchulze, PC-
dc.contributor.authorWang, Y-
dc.contributor.authorXu, A-
dc.contributor.authorSweeney, G-
dc.date.accessioned2017-10-18T08:44:17Z-
dc.date.available2017-10-18T08:44:17Z-
dc.date.issued2017-
dc.identifier.citationAmerican Journal of Translational Research, 2017, v. 9 n. 6, p. 2723-2735-
dc.identifier.issn1943-8141-
dc.identifier.urihttp://hdl.handle.net/10722/248507-
dc.description.abstractLipocalin-2 (also known as NGAL) levels are elevated in obesity and diabetes yet relatively little is known regarding effects on the heart. We induced pressure overload (PO) in mice and found that lipocalin-2 knockout (LKO) mice exhibited less PO-induced autophagy and NLRP3 inflammasome activation than Wt. PO-induced mitochondrial damage was reduced and autophagic flux greater in LKO mice, which correlated with less cardiac dysfunction. All of these observations were negated upon adenoviral-mediated restoration of normal lipocalin-2 levels in LKO. Studies in primary cardiac fibroblasts indicated that lipocalin-2 enhanced priming and activation of NLRP3-inflammasome, detected by increased IL-1β, IL-18 and Caspase-1 activation. This was attenuated in cells isolated from NLRP3- deficient mice or upon pharmacological inhibition of NLRP3. Furthermore, lipocalin-2 induced release of HMGB1 from cells and NLRP3-inflammasome activation was attenuated by TLR4 inhibition. We also found evidence of increased inflammasome activation and reduced autophagy in cardiac biopsy samples from heart failure patients. Overall, this study provides new mechanistic insight on the detrimental role of lipocalin-2 in the development of cardiac dysfunction.-
dc.languageeng-
dc.publisherE-Century Publishing Corporation. The Journal's web site is located at http://www.ajtr.org-
dc.relation.ispartofAmerican Journal of Translational Research-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectLipocalin-2-
dc.subjectPressure overload-
dc.subjectNLRP3 inflammasome-
dc.subjectHMGB1-
dc.subjectToll-like receptor (TLR)-4-
dc.titleLipocalin-2 induces NLRP3 inflammasome activation via HMGB1 induced TLR4 signaling in heart tissue of mice under pressure overload challenge-
dc.typeArticle-
dc.identifier.emailLuo, C: cuiting@hku.hk-
dc.identifier.emailWang, Y: yuwanghk@hku.hk-
dc.identifier.emailXu, A: amxu@hkucc.hku.hk-
dc.identifier.authorityWang, Y=rp00239-
dc.identifier.authorityXu, A=rp00485-
dc.description.naturepublished_or_final_version-
dc.identifier.pmid28670364-
dc.identifier.pmcidPMC5489876-
dc.identifier.scopuseid_2-s2.0-85021299939-
dc.identifier.hkuros281414-
dc.identifier.hkuros292597-
dc.identifier.volume9-
dc.identifier.issue6-
dc.identifier.spage2723-
dc.identifier.epage2735-
dc.identifier.isiWOS:000404548300005-
dc.publisher.placeUnited States-
dc.identifier.issnl1943-8141-

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